This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Long term depression of synaptic strength in Purkinje neurons requires repeated inositol-1,4,5-trisphosphate (InsP3)-mediated Ca2+ release, but the InsP3 receptor, while highly abundant, is extraordinarily insensitive to InsP3 in this cell. Synaptic inputs occur at distinct structures, called spines, that are ca. 15m diameter spheres connected to the dendrite via a narrow neck. The ability of the spine to compartmentalize electrical and chemical signals is poorly understood. We are using this project to drive the development of new electrophysiological modeling capabilities of Virtual Cell.